He hailed from Runan 汝南 (modern Runan, Henan). As a young man he decided to wipe away all corruption throughout the empire. He excelled in the selection of state appointees and was first gentleman of the interior (langzhong), later governor (taishou 太守) of the commandery of Le'an 樂安.
At that time Li Ying 李膺 was regional inspector (cishi 刺史) of the province of Qingzhou 青州. Li Ying was infamous for his severe style of government, so that all his subordinates left their post. Only Chen Fan stayed and ruled with the same methods. When the powerful commander Liang Ji 梁冀 once sent an envoy to Chen Fan with the request to do him a favour, Chen had the man beaten to death. Yet this did not harm his career.
Chen rose the ladder to top positions in the central government, he became chief steward for writing (shangshu 尚書), Director of the Imperial Secretariat (shangshuling 尚書令), Chamberlain for Dependencies (da honglu 大鴻臚), Chamberlain for Attendants (guangluxun 光禄勳), and was finally granted the honourable title of Superior Grand Master of the Palace (taizhong dafu 太中大夫).
In 165, he became Defender-in-chief (taiwei 太尉). At that time he joined with Li Ying in an alliance against the powerful clique of the court eunuchs Su Kang 蘇康 and Guan Ba 管霸. When the young Emperor Ling 漢靈帝 (r. 167-188 CE) acceeded to the throne and Empress Dowager Dou 竇太后 took over regency, Chen Fan also wielded greatest power as Grand Mentor (taifu 太傅).
An internal quarrel among the eunuch leaders Hou Lan 侯覽, Cao Jie 曹節 and Wang Fu 王甫 seemed to be the right moment for Chen Fan and the Empress Dowager's brother Dou Wu 竇武 to annihilate the eunuchs. Yet the Empress Dowager was against their execution. The plan was soon reveiled, and Cao Jie managed to have Dou Wu executed for high treason. Chen Fan decided to fight instead of being exectuted, but he was arrested and killed in prison.